Preventing Rheumatoid Arthritis Requires a Mixed Population of Regulatory T-cells

Rheumatoid arthritis is an autoimmune disorder that occurs when this protection fails and the immune system attacks the synovium, the membrane that lines all the joints of the body. It is a common disorder that causes pain, redness, and swelling around the joints. It has been estimated that approximately one percent of the adult population, worldwide, suffers from rheumatoid arthritis.

Investigators at The Wistar Institute (Philadelphia, PA; USA) used a mouse model of spontaneous autoimmune arthritis. These animals had been genetically engineered to express a “self” molecule - a clonotypic T-cell receptor (TCR) - that induced arthritis by an IL-17–dependent mechanism. The investigators then determined how TCR specificity contributed to Treg activity.

Results published in the May 1, 2012, issue of the Journal of Immunology revealed that administration of polyclonal Tregs suppressed Th17 cell formation and prevented arthritis development. Treatment with Tregs that expressed only the clonotypic TCR did not prevent development of arthritis.

“Our results show, surprisingly, that suppressing the immune response against a single target will not shut down the inflammatory response that causes rheumatoid arthritis,” said senior author Dr. Andrew J. Caton, professor in The Wistar Institute’s tumor microenvironment and metastasis program. “Instead, an array of inflammation-stimulating antigens may be involved in causing the disease, since our study shows that an array of regulatory T-cells is required to temper the immune system’s attack on joints.”

“The big unanswered question of rheumatoid arthritis is ‘why are joints targeted’?” said Dr. Caton. “Of all the tissues in the body, of all the places our immune system could attack, this question remains. One idea is that the immune system is not deliberately attacking joints in patients with rheumatoid arthritis, but the joint inflammation is a side effect of the natural tendency of these cells to accumulate in these areas of the body.”

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The Wistar Institute